The ocular surface is an anatomical and functional unit of the eye that protects the ocular system from external environments and provides a smooth refractive surface for light transmission. As a protective barrier in this unit, the cornea includes closely apposed epithelium and endothelium separated by a collagen-rich stromal tissue that contains keratocytes. At the circumferential margin of the cornea, the corneal epithelium grades into the conjunctiva lined with goblet cells that are responsible for producing the mucus component of the tear fluid. The ocular surface is under the constant influence of a dynamic microenvironment created by spontaneous eye blinking-induced eyelid movements and concomitant spreading of the tear film that permits hydration and lubrication of the cornea and conjunctiva.
The structural, functional and environmental complexity of the ocular surface poses certain technical challenges for in vitro investigation of its physiology and pathology using traditional cell culture models. As a result, certain research in this area has relied on expensive and time-consuming ex vivo or in vivo animal studies that can often fail to model biological responses in humans. These drawbacks of existing models can limit the understanding and the development of new therapeutic approaches to ocular diseases.
One approach to meeting these challenges is to leverage microengineering technologies that provide unprecedented capabilities to control cellular microenvironment with high spatiotemporal precision and to present living cultured cells with mechanical and biochemical signals in a more physiologically relevant context. This has led to the development of microengineered biomimetic systems such as “organs-on-chips” that simulate complex organ-level physiology. This strategy can assist in developing specialized in vitro human disease models that enable reconstitution and quantitative analysis of various biological responses to abnormal microenvironmental signals for ocular disease studies.
Certain in vitro eye models largely fail to fully recapitulate the structural and functional complexity of their in vivo counterparts, and thus have had little to no success in gaining widespread use for practical applications. As a result, current preclinical or non-human testing strategies rely predominantly on time-consuming and costly animal studies using tissue explants or whole animals.